An epistatic mini-circuitry between the transcription factors Snail and HNF4a controls liver stem cell and hepatocyte features exhorting opposite regulation on stemness-inhibiting microRNAs

Preservation of the epithelial state involves the stable repression of EMT program while maintenance of the stem compartment requires the inhibition of differentiation processes. A simple and direct molecular mini-circuitry between master elements of these biological processes, may provide the best device to keep balanced such complex phenomena. In this work, we show that in hepatic stem cell Snail, a transcriptional repressor of the hepatocyte differentiation master gene HNF4, directly represses the expression of the epithelial microRNAs-200c and -34a, which in turn target several stem cell genes. Notably, in differentiated hepatocytes HNF4, previously identified as a transcriptional repressor of Snail, induces the microRNAs-34a and -200a, b, c that, when silenced, causes epithelial dedifferentiation and reacquisition of stem traits. Altogether these data unveiled Snail, HNF4 and microRNAs -200a, b, c and -34a as epistatic elements controlling hepatic stem cell maintenance/differentiation

Bio-ethylene Production: from Reaction Kinetics to Plant Scale

Ethylene production from renewable bio-ethanol has been recently proposed as sustainable alternative to fossil sources. The possibility to exploit diluted bioethanol as less expensive feedstock was studied both experimentally, using different catalysts at lab-level, and through preliminary process design. In this work, a full-scale plant simulation is presented, built on a detailed reaction kinetics. Rate equations for the primary and side reactions are revised and implemented with a process simulation package, using a range of thermodynamic methods as best suited to the different process stages. The catalyst loading within the reactor can be effectively distributed according to the underlying kinetic, and the overall plant layout let foresee the best routes for the material recycles. The detailed reaction modeling and the choice of the thermodynamic models are essential to obtain reliable predictions. Setting a target yield of 105 t/year of polymer-grade ethylene, the reactive section must be fed with 76 t/h of diluted ethanol and operated at 400 \ub0C. 85% of the fed carbon mass is found as ethylene, 12% remains as ethanol and a 2% as longer olefins. Considering also the recycle of ethanol the carbon conversion and recovery increases to the value of 97.6%. The global ethylene recovery is 90.7%: most of the loss takes place in the last stage due to the non-condensable purification and to the adopted strategy of having low reflux ratio \u2013 and then a closed cryogenic balance \u2013 in the last purification column. Full heat integration of the process with upstream bioethanol production and purification sections allows process intensification and consistent energy savings. This newly designed process sets the sustainable ethylene production on a detailed and reassessed computational basis and has been assessed as for Capital and Operational Expenditures and Total Investment costs

Hepatitis C virus production requires apolipoprotein A-I and affects its association with nascent low-density lipoproteins

Background/aims The life cycle of hepatitis C virus (HCV) is intimately linked to the lipid metabolism of the host. In particular, HCV exploits the metabolic machinery of the lipoproteins in several steps of its life cycle such as circulation in the bloodstream, cell attachment and entry, assembly and release of viral particles. However, the details of how HCV interacts with and influences the metabolism of the host lipoproteins are not well understood. A study was undertaken to investigate whether HCV directly affects the protein composition of host circulating lipoproteins. Methods A proteomic analysis of circulating very low-, low- and high-density lipoproteins (VLDL, LDL and HDL), isolated from either in-treatment naive HCV-infected patients or healthy donors (HD), was performed using two-dimensional gel electrophoresis and tandem mass spectrometry (MALDI-TOF/TOF). The results obtained were further investigated using in vitro models of HCV infection and replication. Results A decreased level of apolipoprotein A-I (apoA-I) was found in the LDL fractions of HCV-infected patients. This result was confirmed by western blot and ELISA analysis. HCV cellular models (JFH1 HCV cell culture system (HCVcc) and HCV subgenomic replicons) showed that the decreased apoA-I/LDL association originates from hepatic biogenesis rather than lipoprotein catabolism occurring in the circulation, and is not due to a downregulation of the apoA-I protein concentration. The sole non-structural viral proteins were sufficient to impair the apoA-I/LDL association. Functional evidence was obtained for involvement of apoA-I in the viral life cycle such as RNA replication and virion production. The specific siRNA-mediated downregulation of apoA-I led to a reduction in both HCV RNA and viral particle levels in culture. Conclusions This study shows that HCV induces lipoprotein structural modification and that its replication and production are linked to the host lipoprotein metabolism, suggesting apoA-I as a new possible target for antiviral therapy

Allergic bronchopulmonary aspergillosis in children with cystic fibrosis: An update on the newest diagnostic tools and therapeutic approaches

Cystic fibrosis (CF), the most common autosomal-recessive genetic disease in the Caucasian population, is characterized by frequent respiratory infections and progressive lung disease. Fungal species are commonly found in patients with CF, and among them, Aspergillus fumigatus is the most frequently isolated. While bacteria, particularly Pseudomonas aeruginosa, have a well-established negative effect on CF lung disease, the impact of fungal infections remains unclear. In patients with CF, inhalation of Aspergillus conidia can cause allergic bronchopulmonary aspergillosis (ABPA), a Th2-mediated lung disease that can contribute to disease progression. Clinical features, diagnostic criteria and treatment of ABPA are still a matter of debate. Given the consequences of a late ABPA diagnosis or the risk of ABPA overdiagnosis, it is imperative that the diagnostic criteria guidelines are reviewed and standardized. Along with traditional criteria, radiological features are emerging as tools for further classification as well as novel immunological tests. Corticosteroids, itraconazole and voriconazole continue to be the bedrock of ABPA therapy, but other molecules, such as posaconazole, vitamin D, recombinant INF-γ and Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulators, have been showing positive results. However, few studies have been conducted recruiting CF patients, and more research is needed to improve the prevention and the classification of clinical manifestations as well as to personalize treatment. Early recognition and early treatment of fungal infections may be fundamental to prevent progression of CF disease. The aim of this narrative review is to give an update on ABPA in children with CF

Who comes first. rescheduling endoscopic activity after the acute phase of the Covid 19 pandemic

The current health emergency caused by the COVID19 pandemic has caused an abrupt reduction in all ordinary endoscopic activities [1]. Our endoscopy unit, usually overloaded with procedures, has reduced its activities to immediate urgencies only, as recommended by position statements of many scientific societies [2–4]. After the most critical phase of the emergency, the need to evaluate the relative urgency of the endoscopic procedures was addressed. In our endoscopic academic tertiary referral unit, about 300 endoscopic procedures from March 16 to May 2 were suspended. According to local (hospital) and regional health department indications, outpatient services have been reorganised, by remodulating time slots for procedures, controlling and filtering patients’ access to the unit and reviewing the indications for each single endoscopic procedure programmed but not performed. Procedures initially classified as urgent (by 48 hours, n. 77) and short (by 10 days, n. 68) were directly rescheduled and performed. Furthermore, we decided to interview all the patients of postponed endoscopic procedures by phone calls carried out by trainees, tutored by a senior component of the endoscopy unit. A systematic questionnaire was developed based on the following items: demographic and clinical patient characteristics, current conditions, gastrointestinal signs and symptoms, exam indications and priority classes assigned by the general practitioner or other physicians, time and results of previous endoscopic examinations, laboratory tests, ongoing treatments. Results of the phone interview and any additional clinical documentation e-mailed by the patient was evaluated and archived including date and time of the interview with the patient’s informed consent. Based on the results of the reassessment, patients were rescheduled stratifing the procedures in the following 4 priority cl

Rocket salad: crop description, bioactive compounds and breeding perspectives

Rocket salad is a plant member of the Brassicaceae family whose name encloses species of the Eruca and Diplotaxis genera characterized by leaves with peculiar pungent taste and strong flavour. It has been originated in the Mediterranean area and nowadays is worldwide cultivated and consumed as food condiment and in ready-to-use mixed salad packages. Several other uses are recognized in cosmetics and medicine. This crop represents a valuable source of health benefits due to the presence of a range of health-promoting phytochemicals including carotenoids, vitamin C, fiber, polyphenols, and glucosinolates. These compounds are potentially linked in the prevention of certain diseases and types of cancer. Glucosinolates, represent the major class of compounds in rocket, and their hydrolysis products are responsible of the typical pungent aromas and flavours. Despite the continuous increase of the global consumption during the recent years, few efforts have been carried out in genetic improvement programs aimed to constitute new varieties due to biological and reproductive barriers. In the present article is provided a brief overview of the principal species of rocket salad used in dietary and discussed the qualitative properties as well as the potentiality and constraints for breeding